1. Causative Factors/Risk Factors
1.1. Old Age
1.1.1. Ovarian cancer can occur at any age but is most common in women ages 50 to 60 years.
1.2. Inherited gene mutations
1.2.1. A small percentage of ovarian cancers are caused by gene mutations you inherit from your parents. The genes known to increase the risk of ovarian cancer are called breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2). These genes also increase the risk of breast cancer. Other gene mutations, including those associated with Lynch syndrome, are known to increase the risk of ovarian cancer.
1.3. Family history of ovarian cancer
1.3.1. People with two or more close relatives with ovarian cancer have an increased risk of the disease.
1.4. Estrogen hormone replacement therapy,
1.4.1. especially with long-term use and in large doses.
1.5. Age when menstruation started and ended.
1.5.1. Beginning menstruation at an early age or starting menopause at a later age, or both, may increase the risk of ovarian cancer.
1.6. Infertility
1.7. Polycystic ovarian syndrome
1.8. Endometriosis (increase in risk of clear cell, endometrioid, or low grade serous carcinomas)
1.9. Cigarette smoking (increase in risk of mucinous carcinoma)
1.10. Intrauterine device
1.11. Past use of oral contraceptives
1.12. Past breast feeding (for >12 months)
1.13. Tubal ligation
1.14. Overweight/Obese
1.14.1. Obesity has been linked to a higher risk of developing many cancers. The current information available for ovarian cancer risk and obesity is not clear. Obese women (those with a body mass index [BMI] of at least 30) may have a higher risk of developing ovarian cancer, but not necessarily the most aggressive types, such as high grade serous cancers. Obesity may also affect the overall survival of a woman with ovarian cancer.
1.15. Fertility treatment with in vitro fertilization (IVF) seems to increase the risk of the type of ovarian tumors known as "borderline" or "low malignant potential"
1.16. Having children later or never having a full-term pregnancy
1.16.1. Women who have their first full-term pregnancy after age 35 or who never carried a pregnancy to term have a higher risk of ovarian cancer.
1.17. Using fertility treatment
1.18. Taking hormone therapy after menopause
1.18.1. Women using estrogens after menopause have an increased risk of developing ovarian cancer. The risk seems to be higher in women taking estrogen alone (without progesterone) for many years (at least 5 or 10). The increased risk is less certain for women taking both estrogen and progesterone.
1.19. Having a family history of ovarian cancer, breast cancer, or colorectal cancer
2. Treatments
2.1. Local Treatments
2.1.1. Surgery
2.1.1.1. Staging
2.1.1.2. Debulking
2.1.2. Radiation Therapy
2.2. Systemic Treatments
2.2.1. External beam radiation therapy
2.2.2. Chemotherapy for Ovarian Cancer
2.2.2.1. Usually, the combination includes a type of chemo drug called a platinum compound (usually cisplatin or carboplatin), and another type of chemo drug called a taxane, such as paclitaxel (Taxol®) or docetaxel (Taxotere®). These drugs are usually given as an IV (put into a vein) every 3 to 4 weeks.
2.2.2.2. Some of the other chemo drugs that are helpful in treating ovarian cancer include: Albumin bound paclitaxel (nab-paclitaxel, Abraxane®) Altretamine (Hexalen®) Capecitabine (Xeloda®) Cyclophosphamide (Cytoxan®) Etoposide (VP-16) Gemcitabine (Gemzar®) Ifosfamide (Ifex®) Irinotecan (CPT-11, Camptosar®) Liposomal doxorubicin (Doxil®) Melphalan Pemetrexed (Alimta®) Topotecan Vinorelbine (Navelbine®)
2.2.3. Hormone Therapy for Ovarian Cancer
2.2.3.1. Luteinizing-hormone-releasing hormone (LHRH) agonists
2.2.3.1.1. LHRH agonists (sometimes called GnRH agonists) switch off estrogen production by the ovaries. These drugs are used to lower estrogen levels in women who are premenopausal. Examples of LHRH agonists include goserelin (Zoladex®) and leuprolide (Lupron®).
2.2.3.2. Tamoxifen
2.2.3.2.1. Tamoxifen is a drug that is often used to treat breast cancer. It can also be used to treat ovarian stromal tumors and is rarely used to treat advanced epithelial ovarian cancer. Tamoxifen acts as an anti-estrogen in many tissues in the body, but as a weak estrogen in others. The goal of tamoxifen therapy is to keep any estrogens circulating in the woman’s body from stimulating cancer cell growth.
2.2.3.3. Aromatase inhibitors
2.2.3.3.1. Aromatase inhibitors are drugs that block an enzyme (called aromatase) that turns other hormones into estrogen in post-menopausal women. They don’t stop the ovaries from making estrogen, so they are only helpful in lowering estrogen levels in women after menopause. These drugs are mainly used to treat breast cancer, but can also be used to treat some ovarian stromal tumors that have come back after treatment as well as low grade serous carcinomas. They include letrozole (Femara®), anastrozole (Arimidex®), and exemestane (Aromasin®).
2.3. Targeted Therapy for Ovarian Cancer
2.3.1. Targeted therapy is a type of cancer treatment that uses drugs or other substances to identify and attack cancer cells while doing little damage to normal cells
2.3.2. Bevacizumab
2.3.2.1. Bevacizumab (Avastin) belongs to a class of drugs called angiogenesis inhibitors. For cancers to grow and spread, they need to make new blood vessels to nourish themselves (called angiogenesis). This drug attaches to a protein called VEGF (that signals new blood vessels to form) and slows or stops cancer growth.
2.3.3. PARP inhibitors
2.3.3.1. Olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula) are drugs known as a PARP (poly(ADP)-ribose polymerase) inhibitors. PARP enzymes are normally involved in one pathway to help repair damaged DNA inside cells. The BRCA genes (BRCA1 and BRCA2) are also normally involved in a different pathway of DNA repair, and mutations in those genes can block that pathway. By blocking the PARP pathway, these drugs make it very hard for tumor cells with a mutated BRCA gene to repair damaged DNA, which often leads to the death of these cells.
2.4. Common approaches
2.4.1. Treatment of Invasive Epithelial Ovarian Cancers, by Stage
2.4.1.1. Stage I cancers
2.4.1.1.1. The initial treatment for stage I ovarian cancer is surgery to remove the tumor. Most often the uterus, both fallopian tubes, and both ovaries are removed (a hysterectomy with bilateral salpingo-oophorectomy). The treatment after surgery depends on the sub-stage of the cancer.
2.4.1.1.2. Stages IA and IB (T1a or T1b, N0, M0): The treatment after surgery depends on the way the cancer cells looks in the lab (called the tumor grade). For grade 1 (also called low grade) tumors, most women don't need any treatment after surgery. Women who want to be able to have children after treatment might be given the option of having an initial surgery that removes only the ovary containing the cancer along with the fallopian tube on the same side. For grade 2 (high grade) tumors, patients are either watched closely after surgery without further treatment, or they are treated with chemotherapy (chemo). The chemo used most commonly is carboplatin and paclitaxel (Taxol) for 3-6 cycles, but cisplatin can be used instead of carboplatin, and docetaxel (Taxotere) can be used instead of paclitaxel. For grade 3 (high grade) tumors, the treatment usually includes the same chemotherapy that is given for grade 2 Stage IA and IB cancers.
2.4.1.2. Stage II cancers
2.4.1.2.1. For stage II (including IIA and IIB) cancers, treatment starts with surgery for staging and debulking. This includes a hysterectomy and bilateral salpingo-oophorectomy. The surgeon will try to remove as much of the tumor as possible.
2.4.1.3. Stage III cancers
2.4.1.3.1. Stage III cancers (including IIIA1, IIIA2, IIIB, and IIIC) are generally treated similarly to stage II cancers. First, the cancer is surgically staged and the tumor is debulked (like stage II). The uterus, both fallopian tubes, both ovaries, and omentum (fatty tissue from the upper abdomen near the stomach and intestines) are removed. The surgeon will also try to remove as much tumor as possible. The goal is to leave behind no visible tumor or no tumor larger than 1 cm. When this goal is reached, the cancer is said to have been optimally debulked. Sometimes tumor is growing on the intestines, and in order to remove the cancer, part of the intestine will have to be removed. Sometimes pieces of other organs (like the bladder or liver) may also have to be removed to take out the cancer. The smaller the remaining tumor, the better the outlook will be.
2.4.1.4. Stage IV cancers
2.4.1.4.1. In stage IV, the cancer has spread to distant sites, like the liver, the lungs, or bones. These cancers are very hard to cure with current treatments, but they can still be treated. The goals of treatment are to help patients feel better and live longer. Stage IV can be treated like stage III, with surgery to remove the tumor and debulk the cancer, followed by chemo (and possibly the targeted drug bevacizumab [Avastin]). (If bevacizumab is given, it’s typically continued alone after chemo for up to about a year.)
2.4.2. Treatment for Stromal Tumors of the Ovary, by Stage
2.4.3. Treatment for Epithelial Tumors of Low Malignant Potential
2.4.4. Treatment for Germ Cell Tumors of the Ovary
2.5. Supportive/Palliative Care
3. Common Findings
3.1. Symptoms
3.1.1. Abdominal bloating or swelling Quickly feeling full when eating Weight loss Discomfort in the pelvis area Changes in bowel habits, such as constipation A frequent need to urinate
3.2. Early Stage
3.2.1. Bloating Pelvic or abdominal (belly) pain Trouble eating or feeling full quickly Urinary symptoms such as urgency (always feeling like you have to go) or frequency (having to go often)
3.3. Other symptoms
3.3.1. Fatigue (extreme tiredness) Upset stomach Back pain Pain during sex Constipation Changes in a woman's period, such as heavier bleeding than normal or irregular bleeding Abdominal (belly) swelling with weight loss
4. Diagnostic Tests
4.1. Pelvic Exam
4.1.1. During a pelvic exam, your doctor inserts gloved fingers into your vagina and simultaneously presses a hand on your abdomen in order to feel (palpate) your pelvic organs. The doctor also visually examines your external genitalia, vagina and cervix.
4.2. Imaging Tests
4.2.1. Tests, such as ultrasound or CT scans of your abdomen and pelvis, may help determine the size, shape and structure of your ovaries.
4.3. Blood Tests
4.3.1. Blood tests might include organ function tests that can help determine your overall health. Your doctor might also test your blood for tumor markers that indicate ovarian cancer. For example, a cancer antigen (CA) 125 test can detect a protein that's often found on the surface of ovarian cancer cells. These tests can't tell your doctor whether you have cancer, but may give clues about your diagnosis and prognosis.
4.4. Surgery
4.4.1. Sometimes your doctor can't be certain of your diagnosis until you undergo surgery to remove an ovary and have it tested for signs of cancer.
4.5. Tumor Markers
4.5.1. CA 125
4.5.2. Other Tumor Markers
4.6. Ovarian Cancer Symptom Index
5. Ovarian Cancer and Inflammation
5.1. Ovarian cancer is a type of cancer that begins in the ovaries. The female reproductive system contains two ovaries, one on each side of the uterus. The ovaries — each about the size of an almond — produce eggs (ova) as well as the hormones estrogen and progesterone.
5.2. Ovarian cancer often goes undetected until it has spread within the pelvis and abdomen. At this late stage, ovarian cancer is more difficult to treat and is frequently fatal. Early-stage ovarian cancer, in which the disease is confined to the ovary, is more likely to be treated successfully.
5.3. Inflammation may underlie ovulatory events because an inflammatory reaction is induced during the process of ovulation. Additional risk factors for ovarian cancer, including asbestos and talc exposure, endometriosis (i.e., ectopic implantation of uterine lining tissue), and pelvic inflammatory disease, cannot be directly linked to ovulation or to hormones but do cause local pelvic inflammation. On the other hand, tubal ligation and hysterectomy act as protective factors, perhaps by diminishing the likelihood that the ovarian epithelium will be exposed to environmental initiators of inflammation. Inflammation entails cell damage, oxidative stress, and elevations of cytokines and prostaglandins, all of which may be mutagenic. The possibility that inflammation is a pathophysiologic contributor to the development of ovarian cancer suggests a directed approach to future research
6. Types
6.1. Epithelial tumors
6.1.1. which begin in the thin layer of tissue that covers the outside of the ovaries. About 90 percent of ovarian cancers are epithelial tumors.
6.2. Stromal tumors
6.2.1. which begin in the ovarian tissue that contains hormone-producing cells. These tumors are usually diagnosed at an earlier stage than other ovarian tumors. About 7 percent of ovarian tumors are stromal.
6.3. Germ cell tumors
6.3.1. which begin in the egg-producing cells. These rare ovarian cancers tend to occur in younger women.